The effects of perfusion rate and NG‐nitro‐L‐arginine methyl ester on cirazoline‐ and KCl‐induced responses in the perfused mesenteric arterial bed of rats

Ayotunde S O Adeagbo, Reza Tabrizchi, Christopher Triggle

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Abstract

The purpose of this study was to characterize the effects of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. l‐NAME, in concentrations up to 100 μm, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 μm, it potentiated cirazoline‐induced vasoconstriction at each of the perfusion rates. l‐NAME but not d‐NAME caused a leftward shift of cirazoline concentration‐response curves with a marked increase in the maximal response. The potentiating action of l‐NAME was abolished in arterial beds perfused with a Ca2+‐free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. In endothelium‐intact and ‐denuded preparations, l‐NAME potentiated KCl pressor responses; the endothelium‐independent potentiation of KCl pressor activity was stereospecific, time‐independent and was not prevented by the presence of dexamethasone (0.5 μm) in the perfusion medium. However, l‐NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4–5°C) for 2 days. The absence of K+ in the perfusate did not inhibit the ability of l‐NAME to potentiate α‐adrenoceptor‐mediated pressor responses, and nor did l‐NAME inhibit KCl‐induced vasodilatation in preconstricted arteries. It was thus concluded that l‐NAME does not affect Na+/K+‐ATPase activity. No differences in the potentiating ability of l‐NAME on either cirazoline‐ or KCl‐mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitric oxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; l‐NAME causes potentiation of cirazoline‐ and KCl‐induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats. 1994 British Pharmacological Society

Original languageEnglish
Pages (from-to)13-20
Number of pages8
JournalBritish Journal of Pharmacology
Volume111
Issue number1
DOIs
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Esters
Perfusion
Inbred SHR Rats
Vasoconstriction
Salts
Pressure
Povidone
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Vasoconstrictor Agents
Vasodilation
Viscosity
Nitric Oxide Synthase
Dexamethasone
Endothelium
cirazoline
Arterial Pressure
Nitric Oxide
Arteries
Water

Keywords

  • hypertension
  • N‐nitro‐l‐arginine methyl ester
  • nitric oxide
  • nitric oxide synthase
  • perfused mesenteric arterial bed
  • potassium chloride
  • α‐adrenoceptors

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "The effects of perfusion rate and NG‐nitro‐L‐arginine methyl ester on cirazoline‐ and KCl‐induced responses in the perfused mesenteric arterial bed of rats",
abstract = "The purpose of this study was to characterize the effects of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1{\%} polyvinylpyrrolidone increased as the perfusion rate increased. l‐NAME, in concentrations up to 100 μm, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 μm, it potentiated cirazoline‐induced vasoconstriction at each of the perfusion rates. l‐NAME but not d‐NAME caused a leftward shift of cirazoline concentration‐response curves with a marked increase in the maximal response. The potentiating action of l‐NAME was abolished in arterial beds perfused with a Ca2+‐free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. In endothelium‐intact and ‐denuded preparations, l‐NAME potentiated KCl pressor responses; the endothelium‐independent potentiation of KCl pressor activity was stereospecific, time‐independent and was not prevented by the presence of dexamethasone (0.5 μm) in the perfusion medium. However, l‐NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4–5°C) for 2 days. The absence of K+ in the perfusate did not inhibit the ability of l‐NAME to potentiate α‐adrenoceptor‐mediated pressor responses, and nor did l‐NAME inhibit KCl‐induced vasodilatation in preconstricted arteries. It was thus concluded that l‐NAME does not affect Na+/K+‐ATPase activity. No differences in the potentiating ability of l‐NAME on either cirazoline‐ or KCl‐mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitric oxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; l‐NAME causes potentiation of cirazoline‐ and KCl‐induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats. 1994 British Pharmacological Society",
keywords = "hypertension, N‐nitro‐l‐arginine methyl ester, nitric oxide, nitric oxide synthase, perfused mesenteric arterial bed, potassium chloride, α‐adrenoceptors",
author = "Adeagbo, {Ayotunde S O} and Reza Tabrizchi and Christopher Triggle",
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T1 - The effects of perfusion rate and NG‐nitro‐L‐arginine methyl ester on cirazoline‐ and KCl‐induced responses in the perfused mesenteric arterial bed of rats

AU - Adeagbo, Ayotunde S O

AU - Tabrizchi, Reza

AU - Triggle, Christopher

PY - 1994

Y1 - 1994

N2 - The purpose of this study was to characterize the effects of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. l‐NAME, in concentrations up to 100 μm, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 μm, it potentiated cirazoline‐induced vasoconstriction at each of the perfusion rates. l‐NAME but not d‐NAME caused a leftward shift of cirazoline concentration‐response curves with a marked increase in the maximal response. The potentiating action of l‐NAME was abolished in arterial beds perfused with a Ca2+‐free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. In endothelium‐intact and ‐denuded preparations, l‐NAME potentiated KCl pressor responses; the endothelium‐independent potentiation of KCl pressor activity was stereospecific, time‐independent and was not prevented by the presence of dexamethasone (0.5 μm) in the perfusion medium. However, l‐NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4–5°C) for 2 days. The absence of K+ in the perfusate did not inhibit the ability of l‐NAME to potentiate α‐adrenoceptor‐mediated pressor responses, and nor did l‐NAME inhibit KCl‐induced vasodilatation in preconstricted arteries. It was thus concluded that l‐NAME does not affect Na+/K+‐ATPase activity. No differences in the potentiating ability of l‐NAME on either cirazoline‐ or KCl‐mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitric oxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; l‐NAME causes potentiation of cirazoline‐ and KCl‐induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats. 1994 British Pharmacological Society

AB - The purpose of this study was to characterize the effects of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. l‐NAME, in concentrations up to 100 μm, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 μm, it potentiated cirazoline‐induced vasoconstriction at each of the perfusion rates. l‐NAME but not d‐NAME caused a leftward shift of cirazoline concentration‐response curves with a marked increase in the maximal response. The potentiating action of l‐NAME was abolished in arterial beds perfused with a Ca2+‐free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. In endothelium‐intact and ‐denuded preparations, l‐NAME potentiated KCl pressor responses; the endothelium‐independent potentiation of KCl pressor activity was stereospecific, time‐independent and was not prevented by the presence of dexamethasone (0.5 μm) in the perfusion medium. However, l‐NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4–5°C) for 2 days. The absence of K+ in the perfusate did not inhibit the ability of l‐NAME to potentiate α‐adrenoceptor‐mediated pressor responses, and nor did l‐NAME inhibit KCl‐induced vasodilatation in preconstricted arteries. It was thus concluded that l‐NAME does not affect Na+/K+‐ATPase activity. No differences in the potentiating ability of l‐NAME on either cirazoline‐ or KCl‐mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitric oxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; l‐NAME causes potentiation of cirazoline‐ and KCl‐induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats. 1994 British Pharmacological Society

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KW - nitric oxide synthase

KW - perfused mesenteric arterial bed

KW - potassium chloride

KW - α‐adrenoceptors

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